Ovarian tissue cryopreservation (OTC) in prepubertal girls and young women: an analysis of parents' and patients' decision-making.

PURPOSE: The purpose of this study was to explore the decision-making influences, perceived level of control over decision-making, and mood states of parents and patients who were offered OTC prior to gonadotoxic therapy. METHODS: Parents and patients, at least 12 years old, who required gonadotoxic therapy and were offered OTC prior to therapy, were asked to complete questionnaires. Two validated instruments were also used: the Decision-Making Control Instrument (DMCI) and the Profile of Mood States (POMS). The factors that influenced decision-making were compared using Student's t test, and the scores of DMCI and POMS were compared using the Mann-Whitney test. RESULTS: Thirty-six parents and 16 patients who elected ovarian tissue cryopreservation (OTC) completed questionnaires. Five parents who declined OTC also completed questionnaires. Accepters thought OTC was a good idea and that, in the future, science would enable cryopreserved ovarian tissue to be used to restore fertility (100% parents, 93.8% patients). Among accepters, the desire for genetically related children and prevention of the stress of infertility drove parents' and patients' decisions (90.9 and 100%, respectively). The desire to prevent the stress of infertility was important to parents, but patients were less likely to report that a desire to prevent the stress of infertility factored into their decision-making (66.7 vs. 50.0%; p < 0.001). All respondents felt in control of their decision and displayed low levels of mood disturbance. CONCLUSIONS: Though the decision to undergo experimental OTC is difficult and often urgent, this study suggests that families feel in control of their decision-making and report little emotional disturbance.

In Vitro fertilization and adverse obstetric and perinatal outcomes.

Most IVF-conceived children are healthy, but IVF has also been associated with adverse obstetric and perinatal outcomes as well as congenital anomalies. There is also literature suggesting an association between IVF and neurodevelopmental disorders as well as potentially long-term metabolic outcomes. The main driver for adverse outcomes is the higher risk of multiple gestations in IVF, but as the field moves toward single embryo transfer, the rate of multiple gestations is decreasing. Studies have shown that singleton IVF pregnancies still have a higher incidence of adverse outcomes compared to unassisted singleton pregnancies. Infertility itself may be an independent risk factor. Animal models suggest that epigenetic changes in genes involved in growth and development are altered in IVF during the hormonal stimulation and embryo culture. Further animal research and prospective human data are needed to elucidate the mechanisms by which IVF may contribute to adverse outcomes and to decrease risks.

Dynamic maternal and fetal Notch activity and expression in placentation.

INTRODUCTION: Murine placentation requires trophoblast Notch2, while the Notch ligand, JAGGED1, is reduced in invasive trophoblasts from women with preeclampsia. However, the placental cells with active Notch signaling and expression of other Notch proteins and ligands in placentation have yet to be defined. We sought to identify endothelial cell and trophoblast subtypes with canonical Notch signaling in the decidua and placenta and correlate this to expression of Notch proteins and ligands. METHODS: Notch reporter transgenic mice were used to define canonical Notch activity and immunofluorescence staining performed to characterize expression of Notch1, 2, 3, 4 and ligands, Delta-like 4 (Dll4) and Jagged1 (Jag1) during early placentation and in the mature placenta. RESULTS: Notch signaling is active in maternal and fetal endothelial cells and trophoblasts during early placentation and in the mature placenta. Dll4, Jag1, Notch1, and Notch4 are expressed in maternal vasculature in the decidua. Dll4, Jag1 and Notch1 are expressed in fetal vasculature in the labyrinth. Dll4, Notch2 and Notch4 are co-expressed in the ectoplacental cone. Notch2 and Notch4 are expressed in parietal-trophoblast giant cells and junctional zone trophoblasts with active canonical Notch signaling and in labyrinthine syncytiotrophoblasts and sinusoidal-trophoblast giant cells. DISCUSSION: Canonical Notch activity and distinct expression patterns for Notch proteins and ligands was evident in endothelium and trophoblasts, suggesting Notch1, Notch2, Notch4, Dll4, and Jag1 have distinct and overlapping functions in placentation. Characterization of Notch signaling defects in existing mouse models of preeclampsia may shed light on the role of Notch in developing the preeclampsia phenotype.

VEGFR-1 blockade disrupts peri-implantation decidual angiogenesis and macrophage recruitment.

BACKGROUND: Angiogenesis and macrophage recruitment to the uterus are key features of uterine decidualization; the progesterone-mediated uterine changes that allow for embryo implantation and initiation of pregnancy. In the current study, we characterized the expression of vascular endothelial growth factor receptor-1 (VEGFR-1) in macrophages and endothelial cells of the peri-implantation uterus and determined if VEGFR-1 function is required for decidual angiogenesis, macrophage recruitment, and/or the establishment of pregnancy. METHODS: Expression of VEGFR-1 in uterine endothelial cells and macrophages was determined with immunohistochemistry. To assess the effect of continuous VEGFR-1 blockade, adult female mice were given VEGFR-1 blocking antibody, MF-1, every 3 days for 18 days. After 6 doses, females were mated and a final dose of MF-1 was given on embryonic day 3.5. Endothelial cells and macrophages were quantified on embryonic day 7.5. Pregnancy was analyzed on embryonic days 7.5 and 10.5. RESULTS: F4/80(+) macrophages are observed throughout the stroma and are abundant adjacent to the endometrial lumen and glands prior to embryo implantation and scatter throughout the decidua post implantation. VEGFR-1 expression is restricted to the uterine endothelial cells. F4/80(+) macrophages were often found adjacent to VEGFR-1(+) endothelial cells in the primary decidual zone. Continuous VEGFR-1 blockade correlates with a significant reduction in decidual vascular and macrophage density, but does not affect embryo implantation or maintenance of pregnancy up to embryonic day 10.5. CONCLUSIONS: We found that VEGFR-1 functions in both decidual angiogenesis and macrophage recruitment to the implantation site during pregnancy. VEGFR-1 is expressed by endothelial cells, however blocking VEGFR-1 function in endothelial cells results in reduced macrophage recruitment to the uterus. VEGFR-1 blockade did not compromise the establishment and/or maintenance of pregnancy.

Successful pregnancy following assisted reproduction and transmyometrial embryo transfer in a patient with anatomical distortion of the cervical canal.

Abstract Presented is the case report of a patient noted to have gross distortion of the internal cervical canal during her attempt at embryo transfer following an in vitro fertilization with intracytoplasmic sperm injection (IVF-ICSI) procedure. Multiple attempts at cervical dilation were unsuccessful and the patient was ultimately treated by transmyometrial embryo transfer also known as the Towako method. She successfully achieved a singleton pregnancy and delivered at 41 weeks by primary cesarean section because of arrest of cervical dilation. Transmyometrial embryo transfer represents a viable option for patients with cervical stenosis refractory to conventional methods of navigation or severe anatomical distortion of the internal cervical canal.